The Interaction of Telomeric DNA and C-myc22 G-Quadruplex with 11 Natural Alkaloids
The Interaction of Telomeric DNA and C-myc22 G-Quadruplex with 11 Natural Alkaloids
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端粒 DNA 和 C-myc22 G-四链体与 11 种天然生物碱的相互作用
DOI：
10.1089/nat.2012.0342
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Zhao, Changqi
中科院分区：
文献类型：
--
作者：
Ji, Xiaohui;Sun, Hongxia;Zhao, Changqi
端粒DNA和C-myc 22是与肿瘤发生相关的DNA G-四链体（G4）形成序列。能够促进G4形成并增加其稳定性的配体可以阻止肿瘤细胞增殖，并且被认为是潜在的抗癌药物。本文研究了11种天然生物碱与端粒DNA和C-myc 22序列形成的G4的相互作用。结果表明，血根碱（San）、巴马汀（Palmatine）和小檗碱（Beb）等第一系列（S1）药物能诱导G_4的形成，并能提高其稳定性。第二系列（S2）的蝙蝠葛苏林碱（S2-1）、O-甲基蝙蝠葛碱（S2-2）、O-二乙酰蝙蝠葛苏林碱（S2-3）、蝙蝠葛诺林碱（S2-4）、蝙蝠葛诺林碱（S2-5）、碘化N，N '-二甲基蝙蝠葛碱（S2-6）和碘化N，N'-二甲基蝙蝠葛苏林碱（S2-7）显示类似的稳定能力。我们发现不饱和环C、N+正电荷中心和共轭芳香环是提高S1稳定能力的关键因素，并通过构效关系研究对S2的结构修饰提出了一些建议。此外，我们还发现San和Risin是G（1）细胞周期阻滞剂。推测San通过插入或末端堆积与G4结合。
Telomeric DNA and C-myc22 are DNA G-quadruplex (G4)-forming sequences associated with tumorigenesis. Ligands that can facilitate the formation and increase the stabilization of G4 can halt tumor cell proliferation and have been regarded as potential anti-cancer drugs. In the present study, we have investigated the interaction of 11 natural alkaloids with G4 formed by telomeric DNA and C-myc22 sequences. Our results indicated that sanguinarine (San), palmatine (Pal), and berberine (Beb) of the first series (S1) can induce the formation of G4 as well as increase the stabilization ability. Daurisoline (S2-1), O-methyldauricine (S2-2), O-diacetyldaurisoline (S2-3), daurinoline (S2-4), dauricinoline (S2-5), N,N'-dimethyldauricine iodide (S2-6), and N,N'-dimethyldaurisoline iodide (S2-7) of the second series (S2) showed similar stabilization ability. We found that unsaturated ring C, N+ positively charged centers, and conjugated aromatic rings are key factors to increase the stabilization ability of S1, and we gave some advice on structure modification to S2 through structure-activity study. Besides, we found San and Pal to be cell cycle blocker in G(1). San was speculated to bind to G4 through intercalation or end stacking.